Preliminary findings from an ongoing project indicate that after an episode of uveitis in the copper (Cu) concentration in the intraocular fluids (IOFs) remains higher than in control eyes even after the protein concentration has returned toward normal. At this time the Cu/protein ratio is higher in the IOFs than in control eyes or in blood plasma. The goal of this research proposed is to elucidate the mechansim which determines normal Cu concentrations within intraocular compartments and to determine whether after inflammation the elevated Cu concentration in the IOFs is due to an increased Cu permeability of the blood ocular barriers, or is due to some other mechanism. Alternate mechanisms to be investigated are a prolonged inhibition of an absorptive Cu transport or the loading of some tissue with Cu during the acute phase of inflammation followed by slow Cu release into the IOFs. The amount of Cu present in the free state or bound to proteins, such as ceruloplasmin, in IOFs and present in tissues normally and during various stages of inflammation will be determined. High Cu concentrations can be toxic to cellular membranes and Cu has also been shown to catalyze the breakdown of hyaluronic acid. Thus, prolonged elevation of Cu concentration in the IOFs may contribute to some of the deleterious long-term effects of inflammation on intraocular tissues such as the damage suffered by the transport functions of the ciliary processes. The possible role of Cu in inflammation-induced tissue damage and loss of transport function will be investigated by inducing experimental uveitis in animals whose plasma Cu concentration is greatly reduced by pretreatment with penicillamine and/or Cu free diet and comparing the observed intra-ocular tissue damage to that observed in normal animals or animals which were preloaded with Cu before the induction of experimental uveitis. Finally, the possibility that inflammation causes a prolonged alteration in the intra-ocular fluid concentration of other trace metals such as selenium, manganese, lead, iron, etc., will be investigated. Any trace metal in preliminary experiments that shows a behavior similar to that of Cu will then be studied in detail in a manner similar to that described for Cu. Experimental animals to be used will be rabbits, toads, cats, and primates.